Download Type III Hypersensitivity

Chapter 17
Hypersensitivity
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Types of hypersensitivity
• Type I – immediate Due to IgE binding to Fc
receptors on mast cells and basophils.
• Type II - Antibody-Mediated Cytotoxic Due to
antibody (IgG and IgM) mediated activation of
complement or antibody dependent cell mediated
cytotoxicity (ADCC).
• Type III - Immune Complex–Mediated Due to
accumulation of immune complexes and the
resulting inflammatory response.
• Type IV -Delayed-Type(DTH)Due to activation of
TDTH cell mediated effectors.
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Section II
Type II hypersensitivity
IgG or IgM bind to the Ag on the
surface of target cells to activate
complement, phagocytes, NK cells. As
soon as Ag are cleared, the target cells
and tissue are damaged by abnormal
response.
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I.
Mechanism
1.Ag : on the surface of target cells
2.Ab : IgG and IgM
3.Cell damaged by complement,
macrophage, NK cell et al.
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Ag on the surface of the cell or hapten adsorbed on the
surface of the cell
+
Specific Ab (IgG, IgM)
Complement
activation
Lysis of
target cell
Opsonization
Phagocytose
of target cell
NK cell
phagocyte
ADCC
Stimulate or block
receptor function
Target cell
dysfunction
Target cell damage
The mechanism of type II hypersensitivity
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Mechanisms of
Type II hypersensitivity
B
cell
TH2
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Host
target cell
Complement activation
C1
C2
C4
C3
C3b & C5b
C3a & C5a
C5-C9
Host target cell
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Opsonization
Target cell
C3b
Antibody
Lysosomal
enzymes
Phagocyte
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ADCC
NK
Antibody
Fc
receptor
Perforin and
enzymes
Host Target
cell
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Mechanisms of
Type II hypersensitivity
C activation
Opsonization
ADCC
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II. Disease
1. Blood transfusion reactions
Transfused cells are killed by complement-mediated lysis
Symptoms: Fever, chills, nausea, clotting within vessels and lower back pain.
Increased hemoglobin can lead to a buildup of bilirubin which can be toxic at
high concentrations.
Treatment: Stop the transfusion! Provide diuretic to increase urine output and
reduce buildup of hemoglobin.
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2. Hemolytic disease of the newborn
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• Prevention :Hemolytic
anemia of the newborn can
be prevented by treating the
mother with an anti-Rh
antibody (Rhogam) within
72 hours after the first
Rh+ child was born.
• Rhogam binds to Rh on the
fetal cells to eliminate Rh+
fetal RBC before B cell
activation occurs.
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3. Drug induced hemolytic anemia
Drug (half Ag, penicillin) + membrane of RBC 
produce self Ab  damage RBC
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4. Drug allergy blood cells reduce disease
5. Goodpasture’s syndrome
6. Graves ′ disease
(Thyroid Stimulating Hormone, TSH),
high level thyroxine
Normal:
TSH+TSH-R  induce T3, T4 production
_
Abnormal:
Anti-TSH-R+TSH-R  induce T3,T4 production
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Section III
Type III hypersensitivity
Immune complexes mediated reaction.
In some case, such as high level antigen or
phagocytosis deficiency, body can not clear
these ICs in time. Through activating
complement, neutrophil, platelet, basophil,
the ICs induce erythema, edema, local
tissue necrosis, and neutrophil homing.
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I. Mechanism
1. Ag: soluble Ag.
2. Ab: IgG , IgM.
3.Immune complex.
Big size IC: phagocytosis
Medium size: deposit
Small size: clear with urine
4. Tissue damage
Complement, neutrophil, platelet, et al.
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Ag
+
Ab
Large IC
Small IC
Medium IC
Immune complex , IC
Phagocytosis by phagocytes
Discharged from circulation
Exist in circulation, and deposit
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Immune complex deposit
Activating complement
Mediated mast-cell
and basophil
C3a, C5a, C567
Activating platelet,
star blood coagulation
Chemotaxis
Neutrophil infiltrating
Releasing vasoactive
mediators
Microthrombosis
Releasing lysosomal
Capillary permeability
Tissue ischemia,
necrosis
edema
Vasculitis
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Type III Hypersensitivity
Neutrophil
C3a & C5a
C3
C3b & C5b
C4
C2
C1
C5-C9
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II. Disease
1. Local IC disease
① Arthus reaction
Arthus-like reaction
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② Human local IC disease
接种乙肝后第8天发生的Arthus反应
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2. General immune complex disease
① serum disease
Serum sickness can occur at 7-10 days after anti-serum injection.
Antibodies were produced before antiserum was eliminated.
The binding of antibodies to antiserum forms immune complexes
The deposition of IC causes serum sick: fever, chills, rash, arthritis
and sometimes glomerulonephritis.
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② Systemic lupus erythematosus (SLE)
• Degraded DNA or RNA stimulate B cell to
produce antibody ( anti-nuclear Ab )
• Formation and deposition of Ag-Ab complex
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③ Rheumatoid arthritis
Degraded IgG stimulate B cell to produce IgM antibody
( Rhemotiod factor )
Formation and deposition of Ag-Ab complex
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④ Post-streptococcal
glomerulonephritis
•Streptococcal M protein
stimulate B cell production
•Formation of Ag-Ab
complex and deposition in
kedney
Fluorescence Ab
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Section IV
Type IV hypersensitivity
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• Type IV hypersensitive reaction develop when antigen
activates sensitized TDTH cells
(delayed type hypersensitivity, DTH);
• Th1
• Tc
• The hallmark of a type IV reaction are the delay in time
required for the reaction to develop and the recruitment
of macrophages. The symptoms usually reach maximum
after 24h-72h after touching the antigens.
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I. Mechanism
Antigen: intracellular microbes
Antibody: no
Complements: no
Cells: T cells, macrophages
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Inducing
Antigen
T cell (CD4+,CD8+)
Cytokine
Il-2
CD4+
T cell
IFN-γ
TF
T cell
proliferation
Tissue lesion
TNF-β
Monocyte
infiltration
Exudation
MCF
Re-exposure
MIF
Cytotoxicity
Sensitized T cell
(CD4+,CD8+)
CD8+ T
cell
Killing
target cell
1. Sensitization phase
2. Effector phase
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Mechanisms of type IV hypersensitivity
Mθ
APC
TH1
IL2
TNFα
IFNγ
NO
Mθ
IL2,
TNFα
IFNγ
preTc
Tc
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Type IV Hypersensitivity
perforin
Td Cell
lymphokines
Host Target Cell
altered self -antigens
MΦ
lysosomal enzymes &
O2 radicals
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II. Disease
1. Infectious disease
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2. Contact dermatitis
Contact dermatitis reaction to leather
Contact dermatitis reaction
to mango sap
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Tuberculin test
Tuberculin test is a screening tool for tuberculosis(TB) . 43
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1. Ⅰ、Ⅱ、Ⅲ are mediated by antibody.
2.Complement participate Ⅱ、Ⅲ(must depend on
complent to cause disease).
3.The same allergen in different individual or in the
same individual can cause different type reaction.
4.There may exist two types or more reaction in an
individual.
5.One disease can be elicited by different types
reactions.
Penicillin can induce all four types of hypersensitivity
with various clinical manifestations.
EXERISE
1.Hypersensitivity.
2.Types of hypersensitivity.
3.The mechanisms of type I,II,III,IV reaction.
4. The treatment of type I hypersensitivity
reaction
5. The typical disease of type I,II,III,IV reaction.
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